Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas

Sam S. Yoon, Dan G. Duda, Daniel L. Karl, Tae Min Kim, Avinash R. Kambadakone, Yen Lin Chen, Courtney Rothrock, Andrew Rosenberg, G. Petur Nielsen, David G. Kirsch, Edwin Choy, David C. Harmon, Francis J. Hornicek, Jonathan Dreyfuss, Marek Ancukiewicz, Dushyant V. Sahani, Peter J. Park, Rakesh K. Jain, Thomas F. Delaney

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with ≥5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.

Original languageEnglish
Pages (from-to)1081-1090
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume81
Issue number4
DOIs
StatePublished - Nov 15 2011
Externally publishedYes

Fingerprint

Sarcoma
radiation therapy
Radiotherapy
tumors
cancer
Microvessels
biomarkers
gene expression
Neoplasms
grade
therapy
Recurrence
blood volume
hypertension
Biomarkers
angiogenesis
pelvis
necrosis
Therapeutics
apoptosis

Keywords

  • Angiogenesis inhibitors
  • Bevacizumab
  • Biomarkers
  • Radiotherapy
  • Sarcoma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Yoon, S. S., Duda, D. G., Karl, D. L., Kim, T. M., Kambadakone, A. R., Chen, Y. L., ... Delaney, T. F. (2011). Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. International Journal of Radiation Oncology Biology Physics, 81(4), 1081-1090. https://doi.org/10.1016/j.ijrobp.2010.07.024

Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. / Yoon, Sam S.; Duda, Dan G.; Karl, Daniel L.; Kim, Tae Min; Kambadakone, Avinash R.; Chen, Yen Lin; Rothrock, Courtney; Rosenberg, Andrew; Nielsen, G. Petur; Kirsch, David G.; Choy, Edwin; Harmon, David C.; Hornicek, Francis J.; Dreyfuss, Jonathan; Ancukiewicz, Marek; Sahani, Dushyant V.; Park, Peter J.; Jain, Rakesh K.; Delaney, Thomas F.

In: International Journal of Radiation Oncology Biology Physics, Vol. 81, No. 4, 15.11.2011, p. 1081-1090.

Research output: Contribution to journalArticle

Yoon, SS, Duda, DG, Karl, DL, Kim, TM, Kambadakone, AR, Chen, YL, Rothrock, C, Rosenberg, A, Nielsen, GP, Kirsch, DG, Choy, E, Harmon, DC, Hornicek, FJ, Dreyfuss, J, Ancukiewicz, M, Sahani, DV, Park, PJ, Jain, RK & Delaney, TF 2011, 'Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas', International Journal of Radiation Oncology Biology Physics, vol. 81, no. 4, pp. 1081-1090. https://doi.org/10.1016/j.ijrobp.2010.07.024
Yoon, Sam S. ; Duda, Dan G. ; Karl, Daniel L. ; Kim, Tae Min ; Kambadakone, Avinash R. ; Chen, Yen Lin ; Rothrock, Courtney ; Rosenberg, Andrew ; Nielsen, G. Petur ; Kirsch, David G. ; Choy, Edwin ; Harmon, David C. ; Hornicek, Francis J. ; Dreyfuss, Jonathan ; Ancukiewicz, Marek ; Sahani, Dushyant V. ; Park, Peter J. ; Jain, Rakesh K. ; Delaney, Thomas F. / Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. In: International Journal of Radiation Oncology Biology Physics. 2011 ; Vol. 81, No. 4. pp. 1081-1090.
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AU - Rosenberg, Andrew

AU - Nielsen, G. Petur

AU - Kirsch, David G.

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AU - Harmon, David C.

AU - Hornicek, Francis J.

AU - Dreyfuss, Jonathan

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